Survival, maturation, and function of CD11c(-) and CD11c(+) peripheral blood dendritic cells are differentially regulated by cytokines

Two types of dendritic cells (DC) are circulating in human blood and can be identified by their differential expression of the myeloid Ag CD11c, In th is study, we show that CD11c(-) peripheral blood (PB)-DC correspond to plas macytoid DC of lymphoid tissue not only by their surface Ag expression prof ile but, more impressively, by their peculiar uitramorphology, We also demo nstrate that CD11c(-) and CD11c(+) DC differ in the quality of their respon se to and in their requirement for certain cytokines, Freshly isolated CD11 c(-) cells depend on IL-3 for survival and use autocrine or exogenous TNF-a lpha as maturation signal, leading to the appearance of a highly dendritic phenotype, the up-regulation and redistribution of MHC class II from lysoso mal compartments to the plasma membrane, the increased expression of costim ulatory molecules, and the switch from a high Ag-processing to a low Ag-pro cessing/potent accessory cell mode. Surprisingly, IL-4 efficiently killed f reshly isolated CD11c(-) PB-DC, but did not impair the viability of CD11c() PB-DC and, together with GM-CSF, induced maturation of these cells. A dir ect functional comparison revealed that neo-Ag-modified and subsequently ma tured CD11c(-) but to a lesser extent CD11c(+) DC were able to prime naive Ag-specific CD4(+) T cells. Our findings show that two diverse DC types res pond to certain T cell-derived cytokines in a differential manner and, thus , suggest that suppression or activation of functionally diverse DC types m ay be a novel mechanism fur the regulation of the quantity and quality of i mmune responses.